Evidence map›Paper›PMID 40501659›Full record

ArticlebioRxiv : the preprint server for biology2025

Gut bacterial metabolite imidazole propionate potentiates Alzheimer's disease pathology.

Vaibhav Vemuganti, Jea Woo Kang, Qijun Zhang, Ruben Aquino-Martinez, Sandra Harding, Joseph Lawrence Harpt, Yuetiva Deming, Sterling Johnson, Sanjay Asthana, Henrik Zetterberg and 6 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. The gut as a central hub for multi-organ crosstalk in aging.Cellular and molecular life sciences : CMLS · 2026
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Vaibhav VemugantiDepartment of Bacteriology, University of Wisconsin-Madison; Madison, WI, USA.
Jea Woo KangWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison; Madison, WI, USA.
Qijun ZhangDepartment of Bacteriology, University of Wisconsin-Madison; Madison, WI, USA.ORCID 0000-0002-1003-7355
Ruben Aquino-MartinezDepartment of Bacteriology, University of Wisconsin-Madison; Madison, WI, USA.
Sandra HardingWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison; Madison, WI, USA.
Joseph Lawrence HarptDepartment of Bacteriology, University of Wisconsin-Madison; Madison, WI, USA.
Yuetiva DemingWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison; Madison, WI, USA.
Sterling JohnsonWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison; Madison, WI, USA.
Sanjay AsthanaWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison; Madison, WI, USA.
Henrik ZetterbergWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison; Madison, WI, USA.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Mölndal, Sweden.
Corinne D EngelmanDepartment of Population Health Sciences, University of Wisconsin-Madison; Madison, WI, USA.ORCID 0000-0003-4750-5607
Tyler K UllandWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison; Madison, WI, USA.
Fredrik BäckhedWallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg; Gothenburg, Sweden.
Barbara B BendlinWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison; Madison, WI, USA.
Federico E ReyDepartment of Bacteriology, University of Wisconsin-Madison; Madison, WI, USA.

Funding

Systems Genetics Dissection of Non-alcoholic SteatohepatitisR01DK117850 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Aldons Jake Lusis · 2019 to 2026
$4.6M
Gut barrier function in Alzheimer's DiseaseR01AG070973 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI BENDLIN, BARBARA BRIGITTA, REY, FEDERICO E · 2021 to 2025
$3.9M
ß-hydroxybutyrate inhibition of pathology in Alzheimer's diseaseR01AG083883 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Barbara Brigitta Bendlin, Federico E Rey · 2023 to 2026
$3.8M
Establishing mechanistic links between the gut microbiome and atherosclerosisR01HL148577 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI LUSIS, ALDONS JAKE, REY, FEDERICO E · 2020 to 2023
$2.6M
Gut microbiota and metabolite interactions in atherosclerosisR01HL144651 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE, REY, FEDERICO E · 2019 to 2022
$2.6M
Collaborative Cross of the Microbiome and Metabolic DiseaseR01DK108259 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI REY, FEDERICO E · 2015 to 2019
$2.1M
CRCNS: Repurposing Transformers to Characterize Gut Microbiome & Aging Brain AxisR01AG092220 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Barbara Brigitta Bendlin, Federico E Rey · 2024 to 2026
$1.1M
Maximizing Power in AD Clinical Trials via Multimodal Machine LearningR01AG040396 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI SINGH, VIKAS · 2012 to 2015
$1.1M
Gut microbiome intervention in preclinical and clinical Alzheimer's diseaseR61AG088913 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Barbara Brigitta Bendlin, Federico E Rey · 2025 to 2026
$900k
Exploring the role of Imidazole Propionate on Alzheimer’s Disease and Related DementiasR21AG089348 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI BENDLIN, BARBARA BRIGITTA, REY, FEDERICO E · 2024 to 2025
$408k
NHLBI NIH HHS R01 HL144651NHLBI NIH HHS R01 HL148577NIA NIH HHS R01 AG040396NIA NIH HHS R01 AG070973NIA NIH HHS R01 AG083883NIA NIH HHS R01 AG092220NIA NIH HHS R21 AG089348NIA NIH HHS R61 AG088913NIDDK NIH HHS R01 DK108259NIDDK NIH HHS R01 DK117850
6 · The paper itself

Abstract

The gut microbiome modulates metabolic, immune, and neurological functions and has been implicated in Alzheimer's disease (AD), though the specific mechanisms remain poorly defined. The bacterial metabolite imidazole propionate (ImP) has been previously associated with several AD comorbidities, such as type 2 diabetes and cardiovascular disease. Here, we show that elevated plasma ImP levels are associated with lower cognitive scores and AD biomarkers in a cohort of >1,100 cognitively unimpaired individuals. Metagenomic profiling identified gut bacteria encoding putative orthologs of the ImP-synthesizing enzyme, urocanate reductase (UrdA), whose abundance correlated with both cognitive measures and multiple AD biomarkers. Chronic ImP administration to mice activated neurodegenerative pathways, worsened AD-like neuropathology, and increased blood-brain barrier (BBB) permeability. Complementary

Identifiers

PMID40501659
PMCPMC12157550

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.